One side of “our” difficult problem (i.e. turbulence, did you think about something else?)

The standard response to this question is turbulence – the behaviour of three-dimensional Navier-Stokes equations at fine scales is much more nonlinear (and hence unstable) than at coarse scales.I would phrase the obstruction slightly differently, as supercriticality. Or more precisely, all of the globally controlled quantities for Navier-Stokes evolution which we are aware of (and we are not aware of very many) are either supercritical with respect to scaling, which means that they are much weaker at controlling fine-scale behaviour than controlling coarse-scale behaviour, or they are non-coercive, which means that they do not really control the solution at all, either at coarse scales or at fine. In conclusion, while it is good to occasionally have a crack at impossible problems, just to try one’s luck, I would personally spend much more of my time on other, more tractable PDE problems than the Clay prize problem, though one should certainly keep that problem in mind if, in the course on working on other problems, one indeed does stumble upon something that smells like a breakthrough in Strategy 1,
2, or 3 above. (In particular, there are many other serious and interesting questions in fluid equations that are not anywhere near as difficult as global regularity for Navier-Stokes, but still highly worthwhile to resolve.)